Optimization of chlorotonils towards an orally available treatment

This project prepares the preclinical development of the semi-synthetic chlorotonil derivative dehalogenil for the treatment of bacterial infections caused by Gram-positive pathogens. Dehalogenil impresses with its potent and very rapid antibacterial effect, which is triggered by membrane depolarization and potassium efflux. Further studies on the mechanism of action have revealed secondary targets in both the cell wall and protein synthesis. The unique mode of action opens up new opportunities for the exploratory development of the drug class for community-acquired bacterial infections requiring oral dosing (e.g. skin infections, osteomyelitis), for gastrointestinal diseases (e.g. dominance of enterococci in immunocompromised hospitalised patients) or for so-called step-down therapy (intravenous to oral) in the transition from inpatient to outpatient treatment.